•V 


THE  PREPARATION  OF  THE  ACETYL 
DERIVATIVE  OF  ETHYL  ACETONE 
DICARBOXYLATE 


fJY 


HELEN  MILLAR  HOPKINS 


THESIS 


FOR  THE 


D E G K E O BACHELOR  O F S C I N G E 

IN 


CHEMISTRY 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 


UNIVERSITY  OF  ILLINOIS 


1922 


UNIVERSITY  OF  ILLINOIS 


^■5 


C 


___iLun0 


ig£ 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 

HJELM_JiILIJlRJiOP_KXIlS- 

ENTITLED_JTiiK_RREEARAXIOiI-UF-Tti£-^AU.ET-^L-Deaj.VA-?iVE-OF-ET-MY-L 

A_CETON£_I!iriARB.QXILATiI 

IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
DEGREE  OF  ?AQii?kQ?__Qll_SCXEN_CE 


Instructor  in  Charge 


Ac  Tu^q  HEAD  OF  DEPARTMENT  OF 


51  ""'1 


Digitized  by  the  Internet  Archive 
in  2015 


https://archive.org/details/preparationofaceOOhopk 


Table  of  Contents 


Acknowl edgement 

The  Ileohanism  of  the  isodehydraoetio  Ester  Condensation 

I  Introduction  — 1 

±1  jiixperiraental 

1.  ihe  isodBiiy^i'acetic  ester  condensation 3 

2.  The  condensation  of  malonic  ester  and 

acetoacetic  ester 4 

3.  The  condensation  of  malonic  ester  with  itself  5 

III  Conclusion 6 

IV  bibliography 7 

The  Preparation  of  the  Acetyl  Derivative  of  Ethyl  Acetone 
Dicarboxylate . 

I introduction — 3 

II  Experimental  13 

1.  Preparation  of  ethyl  acetone  dicarboxylate—  13 

2.  The  action  of  crignard's  reagent  on  ethyl 

acetone  dicarboxylate  — 17 

3.  The  action  of  benzoyl  chloride  on  the  magnesium 

compound  of  ethyl  acetone  dicarboxylate-  18 

4.  The  action  of  benzoyl  chloride  on  ethyl  acetone 

dicarboxylate  in  pyridine  solution  19 

5.  The  preparation  of  the  acetyl  derivative  of 

ethyl  acetone  dicarboxylate  19 

III  Conclusion — — — — — — 20 

IV  Bibliography 22 


Introduction 


The  purpose  of  this  investigation  is  to  discover  the 
mechanism  of  the  isodel:iydracetiG  ester  condensation. 

In  the  isodehydracetic  ester  condensation  two  molec- 
ules of  acetoacetic  ester  combine  breahing  out,  first,  a 
molecule  of  v/ater  and  second,  a molecule  of  ethyl  alcohol. 
The  follov;ini_,  explanation  has  been  given. 


The  question  that  arose  is  whether  the  hydrogen  atom 
connected  with  the  carbon  atom  would  be  reactive  enough  to 
combine  with  the  h;^droxyl  group. 

Acetoacetic  ester  exists  in  two  forms,  the  enol 


If  acetoacetic  ester  in  the  enol  form  v.ould  react  with 
the  keto  acetoacetic  ester  which  had  the  assumed  structure 


U 


CF_G— OH 


OH  u. 

CE^irCHO  -OG2E5 


and  the  keto  form 


the  mechan.ism  of  the  reaction 


a 


-2- 


would  be: 


.0 


CH.-G=GH-3- 

® \ 


7 


^-G=GH=G 
C^HgO 


CH„-C-0ii-  CzO 

3,  ^ 

0 

/ 

U-Gii 


GOOG2K5 


3 


the  water  brealciiig  out  first  and  then  the  alcohol - 
I'.'Ialonic  ester  enolized  in  this  way  only 


,G-0H 
/ ^OCoEk 
C-H  “ 


C-OC2H5 
so  if  rnalonic  ester  can  be 
ester  the  second  mechaniS;:: 


inade  to  unite  \7ith  acatoacetic 
is  probably  correct. 


aKPSEiiiEaiTij. 

!The  Acetoacetic  ester  Oondensation 

T?ie  acetoacetic  ester  condensation  has  been  carried 

out  in  the  following  manner'**:  100  g.  of  acetoacetic  ester 

and  250  g.  of  concentrated  siilphuric  acid  v;ere  mixed  to- 

getlier  (no  internal  heating  being  allowed).  Then  the 

mixture  v/as  kept  at  room  temperature  for  10  to  14  days. 

The  mixture  gradually  thickened  and  assumed  a brown  color. 

At  the  end  of  the  period  of  standing  the  mixture  was  poured 

in  500  g.  ice  and  500  g.  of  water.  m/liite  crystals 

probably  a complex  of  unknown  constitution  may  be  repres- 

£ 

ented  by  the  formula  Gi8S-££09.  These  needle-like  crystals 
were  filtered  off  and  washed  with  water  to  remove  the  acid. 
Then  the  filtrate  v/as  extracted  with  ether.  The  crystals 
were  dissolved  in  the  same  solvent  and  the  solutions 
vmshed  with  'water  and  then  extracted  with  10  c.c.  of  sat- 
urated potassium  carbonate  solution.  The  carbonate  broke  up 
the  complex  and  the  potassium  salt  of  isodehydracetic  acid 
dissolved  in  the  water  and  was  separated  from  the  ether. 

The  solvent  now  contained  the  pure  ester.  It  was  dried 
with  calcium  chloride,  the  ether  distilled  off  and  the 
ester  vacuum  distilled.  The  portion  boiling  from  173°-180° 
at  23  mm.  was  collected. 


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The  ester  may  be  brominated  * , using  2 c*c.  bromine  to 

6 g.  oi  the  isodehydracetio  ester  v/hich  had  been  dissolved 
in  15  G.c.  of  chloroform.  After  the  action  was  complete  the 
solution  was  washed  with  sodiuin  sulphite  and  sodirmi  bicarbonate 
solutions,  dried,  and  the  product  recrystallized  from  alcohol, 
after  evaporating  the  chloroform. 

These  crystals  of  monobromo-isodehydracetic  ester  melted 
at  870  0. 

9OOC2H5  QCOG2H5 

p r C - GHr.  G = G - GH05 

/ V ^ / \ 

Hc^GG  ^0  ^ Bro-^H..G-0  0 + H'Br. 

^11  / " \ / 

‘(JH  0=0  GBr-G  = 0 

The  condensation  of  acetoacetic  ester  was  carried  out  in 
order  to  understand  the  manipulation  better.  It  was  found 
that  the  reaction  could  be  completed  in  nine  hours  if  the 
temperature  was  kept  between  35®  and  40®. 

Ivlalonic  ester  and  Acetoacetic  Ester  Gondensation 

250  g.  of  sulphuric  acid  were  added  to  62  g.  of  malonic 
ester  and  50  g.  of  acetoacetic  ester,  and  the  mixture  v;as 
cooled  v/i  th  ice.  This  solution  was  allowed  to  stand  thirteen 
days.  At  the  end  of  that  time  it  was  thich  and  brown.  This 
solution  was  pOured  on  370  g.  of  ice  and  370  g.  of  v;ater. 

No  precipitate  was  obtained.  To  separate  out  the  ester  the 

solution  was  extracted  three  times  v/ith  ether.  This  solution 


-o- 


was  treated  similarly  to  the  solution  obtained  by  the  condensing 
of  acetoacetic  ester*  During  the  vacuuin  distillation  three 
portions  were  collected* 

Dirst  portion  108°  at  27  mm.  - 120°  mm.  at  27  mm. 

Second  ’ ’ 117°  at  40  mm.  - 177°  mm.  at  30  mm. 

Third  ’ ’ 179°  at  39  mm.  ~ 202°  mm.  at  35  mm. 

This  third  portion  v/as  yellow.  On  refractionating  it  the 
liquid  boiling  between  185°  - 192°  at  35  mm.  was  saved.  Six 
grams  v;ere  dissolved  in  pure  dry  chloroform  and  2 c.c.  of 

I 

bromine  v;ere  added,  ^he  solution  v;as  allowed  stand  vd  th 
shading.  Brown  glubiiles  separate  out,  but  standing  disappeared 
These  glubules  v/ere  insoluble  in  chloroform  but  dissolved  in 
alcohol,  vfnen  the  latter  v/as  evaporated,  no  crystals  separ- 
ated out.  This  residue  had  a purple  color.  After  being 
allov/ed  to  stand  for  about  three  months  it  solidified  to 
v/hite  crystals  that  melted  at  81°  C.  The  mixed  melting 
point  of  this  compound  and  the  monobromo-isodehydracetic 
ester  previously  prepared  v/as  83°  C.  This  then  was  ethyl- 
monobromo-isodeliydracetate.  The  chloroform  soluble  portion 
was  washed  vdth  sodium  sulphite  and  sodium  bicarbonate 
solutions  and  then  dried  with  calcium  chloride  and  the  bromo- 
compound  crystallized  from  alcohol.  By  tahing  mixed  melting 
points  this  also  was  found  to  be  etliyl-monobromo-isodehydr- 
acetate. 

The  melting  point  of  the  third  portion  was  between  15° 


!«•  ^ 


I 


i 


-6- 


and  £5^.  vVhen  allowed  to  stand  in  a mixture  of  ice  and  salt 
for  a considerable  length  of  time  { for  about  2 cc*  to  solidify 
it  took  about  2 hours)  the  ester  was  of  a light  yellov;  color 
and  was  waxy. 

Various  other  proportions  were  used  and  experiments  carri- 
ed out  but  no  new  facts  were  discovered. 

Condensation  of  I.Ialonio  Ester  v/ith  Itself 

To  determine  ?;hether  malonic  ester  reacts  with  itself  in 
the  presence  of  sulfuric  acid,  50  g.  of  malonic  ester  v/ere 
treated  with  125  g.  of  concentrated  sulphuric  acid.  The 
reaction  mixture  was  worked  up  as  has  been  described.  After 
purification  a product  boiling  at  199°  C.  was  obtained. 

This  is  the  boiling  point  of  malonic  ester.  To  obtain  further 
evidence  2 c.c.  of  the  product  were  treated  \Yith  10  c.c.  of 
concentrated  ammonium  hydroxide  and  allov/ed  to  stand.  \j'hite 
crystals  melting  at  170°  G.  separated  out.  This  is  the 
melting  point  of  raalonamide  and  shows  that  malonic  ester  is 
unchanged  by  the  action  of  concentrated  sulphuric  acid  in  the 
cold. 

CONCLUSION 

1.  I'.Ialonic  ester  vail  not  react  with  acetoacetic  ester  using 
concentrated  sulphuric  acid  as  the  condensing  agent. 

2.  ilalonic  ester  does  not  condense -with  itself  in  the  presence 
of  concentrated  sulphuric  acid. 


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-7- 


BIBLIOGRAPHY 


1.  Ann. 

222,  4 ( 1883) 

2.  Ann. 

259,  152  (1890) 

3.  Ann. 

222,  25  (1883) 

4.  Ber. 

745  (1893), 

s,* 

r T’  j 


, 1 

t o>‘-  t ) u. 

._'  , * 

‘J!  .' 

■}i  .:&»•. 

i* 

•Jii^  *X 

' " ‘•■r 

*.rUtit  ' 4^ 

J,  r,j  ..'1  / 

l> 

t 4 

>,.  -\U(  . 

« - 7-, 

■\. 

\jf ■' 

. ,r 

tr 

•1 

--.J™  - 

• • *x* 

.11 

> ■ ,,  I 

*> 

\ ' 


’ 

1 .b 

•1  ,.  ■'’ 

* ■'  J 

■ V 

. i ■ 

,iS  ' i 

-8- 

Ihe  Preparation  of  tlie  Aceta^l  Derivative  of  Ethyl 
Acetone  DicarlPOi^-late 

Intro  dn  ctlon 

The  beta  alkyl  and  aiyl  glutaconio  acids  have  been 

made  by  tv/o  general  reactions-  Esters  of  certain  acetylenic 

1 2 

acids  add  malonic  ester  in  the  follov/ing  manner;  * 


On  treatment  of  this  ester  vd.  th  potash  the  potassium  salt 
of  the  desired  acid  is  obtained.  Acidification  then  yields 
the  acid. 


GOOGgHg 

GHg  G5H5G5GGOOG2H5 

GOOG2H5 


GH( GOOGgHg)^ 


GHOOZ 


G H -S 


GHOOG2H5 


IT 


KDE 


GH(  GOOGgHs)^ 


GH  GOOIC 


GHGOOxi 


IT 


GH^GOOH 

E 


2 

The  hydrolysis  by  alkalies  of  alpha  pyrones  also  yields 


the  potassium  salts  of  these  acids. 


p^' 


» . . .> ' • V . M * 

V 


iff 


\v 


■>■ 


: _ : f;S  «^0  .gilij^  V ; 

tr' t>6xgbf^yp:X 

. f 

• i 

i-i.'  vij.' ,-•.  .'Af  : Jt.*  Ijl.  I v-Ja  *■!■<'?■ 


> < 


•s,  M 


; .c^Xo'i  5,f  l.  aJ  ’ :i  c::r.pZ^:fr 


I if'  it>  -,  . . ., 


I . i / 


j'  Jl.  - 


M 


-s- 


GE-G=0 

\ 

GEGOOiC 

n 

GE 

0 

iCOE 

GEa-G 
b , 

\ 

* y 

GrC-GEg 

GOOII 

GEgGOOE 

-h  GHgCOOIC  4-  GgHgOH 

If  the  CQitral  keto  group  of  ethyl  acetone  dicarboxylate 
would  react  with  Grignard’s  reagent,  a compound  would  he 
obtained  which  on  dehydration  and  hydrolysis  should  yield 
a beta  substitution  product  of  glutaconic  acid* 


GKgCOOGgHs 

G=0 

j 

GHgGOOGgHg 
HOE^ 


G^HglilgBr 


GH2G00G2H5 

CgHg-C-OMgBr 

GHgGOOGgEg 


G.Hp--G-OE 
o 0 , 


GHgGOOCgHg 

G-OE 

GE2GOOG2E5 


GH2GOOG2E5 


-EOE 

P O b, 


GHGOOGgEg 


GE..GOOE 

I ^ 


C,H,-C 
6 5 „ 


GEGOOE 


Other  tautomeric  esters,  aceio-acetic  ester^  and  malonic 

ester^  react  in  the  enolic  form  when  treated  with  Grigiiard's 

reagait,  giving  metallic  derivatives  which  on  liydro lysis 

yield  the  original  ester.  The  amount  of  enolization  is 
dependant  u^on  the  concentration,  tempeiature,  and  solvent,^ 


-10- 


Slmilarly  to  acetoacetic  ester  vLi ch  is  the  mono-carboxylio 
ester  of  acetone,  the  dicarhoxyli c ester  is  stron.ly  acid. 

It  dissolves  in  sodium  cerbonate  solution  probably  because 
17^  of  it  exists  in  the  enol  form  in  solution.*^  After  it 
was  found  that  ethyl  acetone  dicarboxyla te  acted  as  an  alcohol 
the  use  of  Grignard’s  reagent  on  the  ester  itself  was  abandoned. 


OHgGOOGgHg 

GOH 

IT 

GHGOOGgHg 


CHgGOOGgHg 

G,H  IlgBr  G-0I.IgBr 

p ^ If 

GHgGOOGgHg 


t-  ^6^6 


HOH 


G-OH 


IT 


GHGOOG^H. 
£ 0 


The  difficulty  with  the  hydroxyl  group  could  possibly  be 
remedied  by  replacing  the  hydrogen  atoms  witha  benzoyl  or  an 
acetyl  group  and  treating  the  resultifig  compound  vd.th  Grignard’s 
reagent. 


GHgGOOGgHg 

’ ^ 

G-OG-G^H^  G^H^.ivlgBr 

GHGOOGgHg  ^ 


GHpGOOGpH. 
C H_-G-0G-G.Er, 
GHzG 

'•OCgHg 


Uli 

HGl 


GH^GOOGgh^ 

GeHg-G-O-GOC.H, 
’ xOH 


Gh=C 


\ 


GHgGOOG^Hg 

rearran.^e  G^Hj^-G-O-GOGgH^ 

' 1 

CKgCOOCgK, 


^ ‘C 


I. 


. • i )jTr 


I 


i:v 


••r 


K 


'1 1 


I 


u i 


■<*  ■ 


JT  ^ - * c.yJU4.?ir:o.‘’3^-'sa 


A* 


.1. 


i i\ 


-11- 


CKCQOH 

IT 

acid-  C^Hr--G 

-- — ^ 6 5 , 

CH  COOH 

There  v/as  the  possibility  also  of  getting 


GH.COOGoH;; 

' ^ .of  ^ 

C-O-G^G.H. 

GHGOOGgig^ 

by  the  action  of  Grignard’s  reagait  on  the  carbonyl  gronp  o^ 
the  benzojrl  radical. 

An  attempt  was  made  to  make  the  benzoyl  derivative  by 

Q 

the  action  of  benzoyl  chloride  on  the  organic  magnesium  compound 


GH2GOOG2K5 

G-OilgBr  G1-G0G  .Hp- 

TT 

GHGOOG2H5 


CHpGOOG^H. 

I ^ ^ o 

G-O-GOG^Hg  -V  I-IgBrGl 

GECOOG^H^ 

S 5 


Ano tiler  method  that  was  tried  was  a general  one  for  tbe 
making  of  0- compounds  from  enolic  esters  and  ketones  by  the 
action  of  the  acid  chloride  on  the  ester  in  pyridine  solution. 
The: compound  with  the  structure^^ 


GKgGOOGgKg 

G-OGOG„H. 

IT  C 0 

GHGOOOgHg 

has  a melting  point  of  57°.  This  substance  has  such  a similar 


I 


-12- 

s tra c tLir e to  that  of  the  desired  corr  - ril  the,t  ii  ;,as  lope.. 
t>u-t  ti' e latter  wo-.  1.1  be  a solid.  In  the  prt.paration  oriy  a 
hig^.1  boiling  nr^terial  v/as  obtained  which  was  decouposed  on 
distilling  so  the  acetyl  derivative  was  prepared  by  the  action 
of  acetyl  chloride  on  the  beng.ene  solution  of  ethyl  acetone 
dicarboxylate  in  the  presence  of  pyridine.  Ihe  active  agent 
in  this  reaction  is 


The  resulting  cornpouiid  has  the  formula: 

GEgCOOGgEg 

/P 

I ^ 

GHOQuO  E 
2 5 

k simple  tvjst  to  distinguish  ett.yl  acetone  dicarboxylate 
from  the  beta  derivatives  of  glataccnlc  ester  can  be  made 
by  adding  a dilute  solution  of  copper  acetate  to  an  ether 
solution  of  the  ester.  In  the  presence  of  a snail  anount  of 
the  etbpl  acetone  dicarboip"la  te  the  ether  ia^  er  is  a bluish^ 
green  and  in  the  presence  of  a larger  amicunt  of  ester^^ 
blue  bushp  crystals  separate  and  can  be  reerps ta llized  from 
alcohol.  The  crys  uals  .elt  at  14.a°  G.  aad  have  the  . ormula 

GEpGOOGpE^  Gn  GOOG.rl. 

’ I S 2 t) 

0-0 Gu-O-G 

’ IT 

Gir:G0UG£E5  GhG00G„E^ 

o 


-is- 

12 

The  Preparation  of  Ethyl  Acetone  Dicar'box.ylate* 

Three  preparation  of  this  ester  were  niade  using  the 
following  directions: 

"In  a 5 1.  glass  jar  eq.uipped  v;i  th  a mechanical  stirrer 
and  coo  led  v/ith  ice  and  salt,  place  9 Ih.  of  fuming  sulphuil  c 
acid  (20^;.  Add  slowly  in  small  portions  1000  g.  of  citric 
acid  so  that  the  temperature  of  Hie  reaction  does  not  rise  above 
0°  until  about  l/S  of  the  acid  has  been  added,  and  not  above 
10*^  until  aboLit  2/3  of  the  citric  acid  has  been  added,  the 
final  temperature  should  be  about  20°.  After  the  greater  part 
of  the  citric  acid  has  been  added  (about  4/5)  and  the  temper- 
ature has  risfen  nearly  to  20°  there  will  be  a vigorous 
evolution  of  gas  and  much  foaming.  After  this  vigorous 
evolution  has  subsided  the  temperature  will  have  fallen  to 
15°,  the  remainder  of  the  acid  ms^y  be  added  at  one  time,  and 
the  mixture  stirred  until  foaming  has  ceased.  The  jar  should 
then  be  remolded  from  the  cooling  mixture  and  the  temperature 
allov/ed  to  rise  to  30°  and  kept  at  this  temperature  until  all 
evolution  of  gas.  has  ceased,  as  will  be  seen  by  interrupting 
the  stirring,  when  after  a minute  or  so  the  mixture  will 
appear  as  a clear,  brown  liquid  vdth  veiy  fevv  gas  bubbles. 

The  jar  is  now  placed  in  a cooling  mixtui-e  and  the 

teraperetare  allowed  to  sink  to  10%^.  oVd  then  2400  g,  of 
finely  ground  ice  added  in  small  portions  so  that  the  temperatur 


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-14- 


of  the  mixture  never  rises  above  40°.  The  first  portions  of 
ice  must  be  added  slowly  but  after  the  acid  is  somewhat 
diluted  it  may  be  added  more  rapidly.  After  all  the  ice  has 
been  added  the  mixture  is  cooled  to  10°  or  0*^,  then  filtered 
as  rapidly  as  possible  oit  a funnel  fitted  with  a filtrose 
plate  sealed  with  sodium  silicate,  pressed  down  hard  and 
suched  as  diy  as  possible. 

The  acetone  dicarboxylic  acid  should  now  appear  as  a slight- 
ly pinkish- v;hite  flaky  material.  After  being  well  pressed 
and  sucked  dry,  it  is  washed  with  ethyl  acetate  by  stirring 
with  sufficient  of  the  acetate  to  wet  the  whole  of  the  precip- 
itate in  a beaker  and  again  filter.  The  process  is  repeated 
v/ith  more  acetate. 

The  yield  is  430-460  grams. 

The  acid  is  mixed  with  an  equal  weight  of  absolute  alcohol 
v;hich  has  previously  been  saturated  with  dry  hydrogen  chloride 
and  the  mixture  unarmed  gently  on  the  water  bath  to  40°  with 
frequent  shaking  until  all  of  the  acid  is  dissolved.  The  flask 
is  then  closed  v/ith  a stop,  er  bearing  a GaCl,  tube  and  allov/ed 
to  stan-d  over  night. 

The  contents  of  the  flask  are  now  oil  an  equal  v/eight 

of  ice  and  the  ester  layer  separated.  The  alcohol-v/ater  layer 
is  extracted  several  times  with  ether. 

The  ether  layer  is  added  to  the  ester  layer  and  the  ether 
solution  washed  with  10/3  ITagCO^  solution  until  free  from  acid 


-15- 


then  with  dilute  and  finally  twice  v/ith  water* 

The  ester  layer  is  heated  on  the  water  Data  under 
diminished  pressure  as  long  as  anything  distils  over.  This 
process  removed  the  watei",  alcohol  and  ether*  Tre  es-ter 
is  then  vacuum  distilled,  collecting  the  fraction  from  120®- 
180°  at  50  mm.  The  fraction  is  again  vacu^nm  distilled  collecting 
the  fraction  "boiling  from  155*^  - 162°  at  ^50  mm. 

The  yield  is  70  - 75^  of  the  weight  of  the  acid”. 

The  reaction  is  as  follows: 

CH,,000H  GH  GOOH 

, C I c 

GOHGOOE  H SO  G=0  + GO  -+•  EOK 

GEgGOOE  GEgGOOE 

Poliowing  these  directions  it  was  found  that  the  tempefature 
did  not  rise  as  rapidly  as  vas  indicated.  ."nen  the  jar  v;as 
removed  from  the  freezing  mixture  it  took  almost  two  nours 
for  the  temperature  to  rise  to  30°,  "but  if  the  jar  ’was  sur- 
rounded with  warm  water  much  time  was  saved. 

ifiien  the  acid  was  washed  v/ith  ethyl  acetate  just  enough 
was  added  to  mcisten  the  acid,  the  yield  of  product  v/as  inc_eased 
and  there  v/as  no  noticeable  decrease  in  the  amount  of  ester 
obtained.  It  v/as  possible  to  keep  the  acid  without  decompositior 
if  the  temperature  was  kept  at  about  10°. 

After  the  ester  was  prepared  the  separation  of  the  ether 
layer  became  increasingly  difficult  because  of  tarry  material 


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-i6- 


arui  emulsions.  The  ester- ether  layer  v/as  filtered  and  ammonium 
sulphate  added  to  the  soliition  and  no  farther  difficulty 
was  expert enced- 

In  fractionating  the  ester  its  boiling  point  was  found 
to  be: 

135°  - 137°  at  10  -12  mm. 

175°  - 180°  at  75  mm 

142°  at  17  mm. 

Decomposition  took  place  above  180°  and  the  pressure  rose 
^0  100  mm. 

5 lb.  fuming  suifuric  acid  (20fo) 

Prepe^ration  I 

3 lb.  fuming  sulfuric  acid  { 20'/o) 

330  g.  citric  acid. 

1800  g.  ice. 

Yield  of  acid  173  g. 

173  g.  alcohol  and  hydrogen  chloride. 

Yield  of  ester  65  grams. 

Preparation  II 

6 3/4  lbs.  fuming  sulphuric  acid  ( 20;b) 

750  g.  citric  acid 

1800  g.  ice 

Yield  of  acid  232g. 

255  g.  alcohol  and  hydrogen  chloride 

Yield  of  ester number  of  grams  not  Imov/n. 


-17- 


Preparation  III 

6 3/4  It),  fuming  sulphuric  acid  ( 20;4) 

750  g.  citric  acid 

1800  g.  ice 

yield  of  damp  acid  550  g.  prohabUy 

460  dryfacid 

520  g.  alcohol  and  hydrogen  chloride 

Yield  of  ester  200  g. 

The  theoretical  yield  of  the  acid  using  750  g.  of  citric 
acid  is  618  g.,  and  the  ester  855g. 

Action  of  Orignard*s  reagent  on  Ethyl  Acetone  Dicarhos^/late 

The  ratio  of >9  mols  of  phenyl  magnesium  bromide  to  one 
mole  of  ethyl  acetone  dicarboxyla te  was  used  to  see  if 
Grignard’s  reagent  would  attach  the  middle  heto  group.  15  g. 
of  ester  in  15  c.c.  of  anhydrous  ether,  v.hich  has  stood  in 
the  cold  to  decrease  the  enolizaticn,  was  treated  v.ith.  the 
organic  magnesium  halide,  'ilien  the  latter  bit  the  ester  a 
white  precipitate  formed.  Shortly  afterwara.s  the  solution 
became  brovn.  The  mixtare  was  refluxed  tv.o  hours  and  on 
standing  v;hite  crystals  separated  out.  The  mixture  was 
poured  on  50  g.  of  ice  and  50  g.  of  water  and  10  c.c.  (l:l) 
sulfuric  acid.  The  ester  and  water  Inyers  were  separated 
and  the  ester  layer  was  v/ashed  with  5'fo  sulphuric  acid  and 
then  with  water.  The  water  layers  were  extracted  with  ether 


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-18- 


After  mixing  the  ester  and  ether  portions  the  solution  was  dried 
v,l  th  anhydrous  sodium  sulfate  and  the  solvent  distilled  off. 
Distilling  in  a vacuum  9 g.  of  ester  and  about  3 g.  of  residue 
were  obtained.  Tr.e  latter  was  proved  b;^  saponification  to  be 
decomposition  priducts. 

The  ester  Vt/as  fractionated  and  a colored  portion  of  3 g. 
was  collected  that  boiled, giving  off  violet  vapors,  over  a 
vade  range  of  temperature  (up  to  160^)  under  60  mm.  pressure. 
From  160^  to  180°  at  70  mm.  a 5 l/£  g.  portion  of  clear  liquid 
distilled.  The  first  frac  tion  was  shown  by  the  copper  acetate 
test  to  contain  a very  small  a’“::ount  of  ethyl  acetone  dicarbox- 
ylate  and  the  second  portion  to  be  almost  wholly  this  ester. 

The  Action  of  Benzoyl  Chloride  on  the  I.la,  :nesiurn  Compound  of 

Ethyl  Acetone  Dicarbox;;:late _ 

One  equivalent  of  the  Grignard  reagent  v;as  dropped  on  an 

equivalent  of  ethyl  acetone  dicarboxylat e in  solution  in 

anhydrous  ether  which  v/as  srjrrounded  by  ice.  Then  one 

equivalent  of  benzoyl  chloride  in  ether  solution  v/as  added. 

After  standing  for  half  an  hour  the  contents  of  the  flesh  were 

emptied  into  ice  and  a small  amount  of  acid.  The  precipitate 

that  was  present  dissolved.  The  water  and  ether  layers  v/ere 

separated  and  the  latter  v/ashed  with  v/ater,  sodium  carbonate 

solution,  and  again  Mth  water.  A v/hite  oily  emulsion  in  the 

ether  resulted.  On  evaporation  of  the  solvent  and  recrystal- 
lizatioii  of  the  product  from  water  the  substance  was  found  to 


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-19- 

be  benzoic  acid. 

Action  of  Benzojtl  Chloride  on  lithyl  Acetone  .bicarboxjlate  in 

Q 

Pyri dine  s olnt i on. 

10  g.  of  ethyl  acetone  dicarbosylat e in  30  c.c.  of  pyridine 

v/ere  treated  with  7 g.  of  benqoyl  chloride.  This  mijctare  was 

allowed  to  stand  over  night  and  then  poured  on  a calculated 

amount  of  hydrochloric  acid  to  combine  with  the  pyridine. 

The  solution  was  extracted  with  ether  and  the  latter  washed 

v/ith  sodium  carbonate  solution  until  alhaline.  This  last 

extraction  removed  the  benzoic  acid  that  pioved  troublesome 

if  present-  The  acid  is  formed  by  the  slov/.hyrolys is  of  the 

acid  chloride.  After  washing  the  ether  wl  1h  water  if  was 

dried  with  anhydrous  sodium  sulphate,  and  the  solvent 

evaporated.  On  fractionating  a portion  was  collected  from 

to 

100°  - 125°  at  7 mm.  pressure.  This  was  proved  not^be 
ethyl  acetone  dicarboxyla te  by  the  copper  acetate  test.  The 
second  fraction  v/as  collected  between  176°  - 196°  at  7 mm. 
pressure.  It  liad  no  definite  boiling  point. 

The  Preparation  of  the  Acetyl  Derivative  of  Ethyl  Acetone 

Oicarbox:>~lat  e. 

Several  attempts  were  made  to  make  the  acetyl  derivative. 

In  the  most  successful  preparation  the  materials  rsed  v/ere: 

25  g.  etliyl  acetone  dicarboxylate. 

83  cc.  dry  benzene 


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-20- 


10.5  g.  acelyl  clilorid^ 

11  S*  Pyridine 

The  ester  was  dissolved  in  the  benzene  and  the  acet^^l  chloride 
added.  The  mixture  was  kept  cool  but  not  cold  enough  to 
freeze  the  benzene.  The  pyridine  was  added  drop  by  drop. 

The  solution  v;as  allov/ed  to  stand  laalf  an  hour  and  then  was 
poured  into  250  c.c.  of  v;ater  v;hich  contained  the  calculated 
amount  of  hydrochloric  acid  to  react  with  tie  pyridine. 

After  separating  tie  benzene  la.yer  from  the  water,  the  latter 
v/as  v/ashed  ^vith  very  dilute  hydrochloric  acid  solution,  v/ith 
sodium  carbonate  solution,  and  finally  dried  with  anhydrous 
sodium  sulphate.  The  benzene  was  evaporated  off  and  'the 
remaining  liquid  was  vacuum  distilled. 

i^irst  fraction  55®  - 132®  at  7 mm. 

Second  Fraction  127®  - 136.5®  at  7 mm. 

Third  fraction  residue 

The  second  portion  was  redistilled  and  the  constant  boiling 
portion,  129®  - 132®  at  5 l/2  mm.  pressure,  was  collected, 
and  a carbon  and  hydrogen  determination  made. 

17eight  of  sample  .1635  g. 

Weight  of  v;ater  .1035  g. 

V/eight  of  carbon  dioxide  .3289  g. 


Theoretical 


Sample 


54.86^ 


54.09/O 


Carbon 


Hydrog  en 
7.03 

6.56^ 


The  product  was  proved  not  to  be  ethyl  acetone  dicarboxylate 


-21- 


by  the  copper  acetate  test.  This  compound  is  then  the  acetyl 
derivative  of  ethyl  acetone  dicarhoxylate. 

CH^GOOC^Hp. 

I P xi  O 

C-O-O-GH, 

It  o 

GHGOOGgHg 

GQhGLUSIQITS 

1.  Ethyl  acetone  dicarhoxylate  as  is  the  case  v/ith  other 
tautomeric  esters;  reacts  in  the  presence  of  Grignard’s 
reagent  as  an  alcohol. 

2.  The  acetyl  derivative  of  the  enol  form  of  the  ethyl 
acetone  dicarhoxylate  has  been  prepared. 


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BiblioKraphy 

1.  J.pr.U)  490#  22,U894; 

2.  J.C.S.  73,  1015  U898) 

3.  Ann.  222,  31  (1884) 

4.  0.73  (1),  1197  (1902) 

5.  J.A.C.  115,  1208-9  (1919) 

6.  Ann.  380,  212-42  (3911) 

7.  Meyer  and  Jacobson,  Lehrbuch  der  Organischen  Chemie,  1217 

8.  A.C.J.  31,  653  (1904) 

9.  Ber.  37,  3929  (1905) 

10. 

Ann.  363,35,  (19u8) 

11. 

Ann.  261,  176  (1891) 

12.  Marvel  and  Chiles,  unpublished  work. 


